DESCRIPTION (Adapted from the application) Recent advances in basic research techniques have led to an explosion of information and interest in the role of gastrointestinal peptides in health and disease. The function of these peptides has been shown to extend beyond their classical role as hormones to include actions as paracrine effectors, neurotransmitters, growth factors and cytokines. Peptides are well known to have a myriad of actions in the gastrointestinal tract, but also to have profound influences on the function of most of the body?s organ systems. The ubiquitous distribution and myriad actions of gut peptides served as the catalyst that culminated in the formation of the University of Michigan Gastrointestinal Peptide Research Center; a successful multidisciplinary group of investigators that crosses traditional clinical disciplines and scientific boundaries. Advances in cell biology, biochemistry, and molecular biology have provided tools with which the genetic or molecular links between peptides and clinically relevant disorders of digestive function may be identified. However, because of the disparate demands of clinical and basic science, relatively little progress has been made in approaching some of these questions in a unified and broad-based manner. Therefore, one of the principal goals of the Peptide Center is to promote interactions between clinical and basic scientists with the aim of catalyzing collaborative research efforts directed at elucidating the role of gut peptides in molecular pathophysiology of digestive diseases. The Center, through its Core laboratories and support of innovative Pilot/Feasibility projects, has provided expertise, technical and financial support that enabled investigators to broaden the scope of their research. Indeed, many of the Pilot projects have resulted in ongoing research initiatives. In the previous funding period the seven Cores (RIA/Radioligand, Tissue Culture, Molecular Biology, Histochemistry/Morphology, Biochemistry, Cell Biology and In vivo Studies) focused their activities on the primary goals to serve as an intellectual resource, to house specialized equipment and innovative technology, and to perform numerous services for Center investigators. Extensive use of these resources greatly expanded and enriched the base of investigators that are involved in gastrointestinal research at the University of Michigan. The current application requests support for six Core laboratories. The updated responsibilities for each Core reflect advances in our ability to study the biochemical and molecular mechanisms of actions of peptides in integrated models. In summary, the Peptide Center has galvanized the activities of a large number of researchers who investigate the actions of gut peptides at the University of Michigan, as well as attract new investigators to this field of research. Through the current application, we are seeking to continue and expand the Center with the hope that together the group will approach questions of fundamental importance in the pathophysiology, diagnosis, and treatment of digestive diseases in man.